Overall survival of patients with recurrent pancreatic cancer treated with systemic therapy: a retrospective study

Abstract

Background: Only a few patients with pancreatic ductal adenocarcinoma (PDAC) recurring after curative resection and peri-operative (neoadjuvant and adjuvant) therapy are included in clinical trials of metastatic PDAC. As such, there is a paucity of data to guide treatment after relapse, and patients are treated similarly to those with de novo metastatic PDAC (mPDAC). We evaluated the patterns of chemotherapy use and over-all survival (OS) in patients with recurrent PDAC (rPDAC) following curative therapy.

Methods: In this retrospective study, the Indiana University pancreatic cancer database was used to identify patients with PDAC who underwent curative resection and subsequently developed recurrence. Demographics, tumor and treatment characteristics were collected. Patients were broadly divided into those who received chemotherapy for rPDAC and those who did not. Patients in the former category were further subdivided into those who received single agent therapy, any standard combination therapy (5-fluorouracil/irinotecan/oxaliplatin combination or gemcitabine/nab-paclitaxel) and those who received non-standard combinations. Survival analysis was performed by the Kaplan-Meier method. Log rank tests were used to determine differences in survival between treated rPDAC patients and those not treated. Cox regression analysis was employed to evaluate factors associated with OS.

Results: We identified 435 patients with resected PDAC treated between 2008 and 2014. Two hundred and twenty-three patients (51.2%) were diagnosed with rPDAC. Of these, 140 patients (63%) received chemotherapy whereas 71 patients (32%) did not receive chemotherapy. The 74 patients (53%) who received any standard, approved multiagent combination regimen had a median OS of 14 months compared to 8 months for the 47 patents (34%) who received other non-standard combinations and the 19 (13%) who received single agent therapy (P = 0.029). Multivariate cox regression analysis showed that margin negative resection, peri-operative therapy, radiotherapy and the use of any chemotherapy for rPDAC were associated with improved OS.

Conclusion: Our findings support the use of standard approved multi-agent therapy in rPDAC. Patients derive significant benefit from these standard combination therapies with median OS that is comparable to what is observed with treatment for de novo mPDAC.

Keywords: Combination chemotherapy; FOLFIRINOX; Gemcitabine-nab paclitaxel; Metastatic pancreatic cancer; Recurrent pancreatic cancer; Recurrent pancreatic ductal adenocarcinoma.

Fig. 1

Flow chart showing the study population. Four hundred and thirty-five patients were identified from the database of patients with localized and resected pancreatic cancer. Of the 223 with recurrent pancreatic ductal adenocarcinoma, 140 received systemic hemotherapy and 71 did not

Fig. 2

Overall Survival analysis of rPDAC patients who received chemotherapy compared to those who did not. The median OS for those who received chemotherapy (broken lines) was 10 months compared to 3 months without chemotherapy (solid line). Log—rank p < 0.0001

Fig. 3

Overall Survival Analysis of rPDAC patients who received different chemotherapy regimens. Patients who received standard combination; FOLFIRINOX and /or gemcitabine- nab-paclitaxel (tiny broken lines) compared to those who received other non-standard combinations (larger broken lines) and single agent therapy (solid line). The median OS; standard combinations was 14 months, non-standard and single agent therapy, 8 months. Log-rank p = 0.0295

Fig. 4

Overall survival analysis of rPDAC patients who received *peri-operative chemotherapy compared to no peri-operative therapy. The median OS for patients who received peri-operative chemotherapy (broken line) was 8 months and 5 months for those who did not receive perioperative chemotherapy (solid line). Log—rank p < 0.2206. ^*perioperative (both adjuvant and neoadjuvant therapy)